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Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England..
NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England..
Univ Utah, Sch Med, Dept Internal Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA..
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2017 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 14175Article in journal (Refereed) Published
Abstract [en]

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P = 5.04 X 10 (-) (13)), 1q42.13 (rs41271473, P = 1.06 X 10 (-) (10)), 4q24 (rs71597109, P = 1.37 X 10 (-) (10)), 4q35.1 (rs57214277, P = 3.69 X 10 (-) (8)), 6p21.31 (rs3800461, P = 1.97 X 10 (-) (8)), 11q23.2 (rs61904987, P = 2.64 X 10 (-) (11)), 18q21.1 (rs1036935, P = 3.27 X 10 (-) (8)), 19p13.3 (rs7254272, P = 4.67 X 10 (-) (8)) and 22q13.33 (rs140522, P = 2.70 X 10 (-) (9)). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.

Place, publisher, year, edition, pages
2017. Vol. 8, article id 14175
National Category
Cancer and Oncology
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URN: urn:nbn:se:uu:diva-316933DOI: 10.1038/ncomms14175ISI: 000393338200001PubMedID: 28165464OAI: oai:DiVA.org:uu-316933DiVA, id: diva2:1079678
Funder
NIH (National Institute of Health), NO1-CO-12400 K08CA134919 CA167552 CA149445 CA098122 CA186107 CA87969 CA49449 HHSN261201000026CSwedish Cancer Society, 02 6661Wellcome trustAvailable from: 2017-03-09 Created: 2017-03-09 Last updated: 2017-11-29Bibliographically approved

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